1. SNOMED CT, Synoptic Observables and Clinical Genomics
James R. Campbell MD
W. Scott Campbell PhD
Departments of Internal Medicine and Pathology
University of Nebraska Medical Center

2. Acknowledgements Geoffrey Talmon MD Audrey Lazenby MD
Allison Cushman-Vokoun MD PhD
Raj Dash MD
Mary Kennedy
Observable project team
iPaLM SIG; RCP, RCPA, Pathologists of Sweden

3. Outline
Phase 1
Observables development for Molecular Pathology (MP) in Synoptic reports
Observables development for Anatomic Pathology (AP) in Synoptic reports
Publication and draft comments
Phase 2
International collaboration and standardization

4. UNMC: Project for structured encoding of Pathologist cancer reports
Objective: Detailed structured reporting of all anatomic and molecular pathology observations for all CAP synoptic cancer worksheets (82 types of malignancies)
Proposal: Phase 1- Analyze detailed semantics of CAP worksheets; apply harmonized concept model to develop terminology requirements; deploy as real-time structured reporting from COPATH system interfaced to tissue biobank and EPIC
Tooling: Nebraska Lexicon© extension namespace; SNOWOWL authoring platform; SNOMED CT International + US Extension + Observables Technology preview; ELK DL classifier
Phase 2 - Expand project in collaboration with RCP, RCPA, Sweden, ICCR to include international standardization of cancer synoptic reporting

5. SNOMED CT Content Extensions for Pathology
Body structures>>Cell structures>>Nucleotide sequences and Named Genes
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP methods
Qualifiers>>Measurement Properties>>AP and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular genetic observation results and disorders

6. Molecular pathology (MP) Use Case
Iteratively analyze semantics in CAP work sheets; define content and FSN for observables; review with iPaLM domain experts for subject matter
Extend the SNOMED CT concept model and add content in Body Structures and Substances to include genes and proteins needed for MP use case
Bind Genes and proteins by reference to NCBI ontologies and classify
Vet analyzed content with Observables project for definition; define use cases and develop consensus templates for application of concept model; document for editorial guide

7. MP: CAP Checksheet Source Material

8. Analyze semantics
“Tumor expression of BRAF protein as measured by immunohistochemistry stain”

9. 6.1.1.1 Extend the SNOMED CT concept model to include genes and proteins
Reference material at National Center for BioOntologies

10. 6.1.1.1 Extend the SNOMED CT concept model to include genes and proteins
Add genes to body structures and proteins to substances as required by use case

11. 6.1.1.1 Extend the SNOMED CT concept model to include genes and proteins
Add genes to body structures and proteins to substances as required by use case

12. SNOMED CT Content Extensions for MP
Body structures>>Cell structures>>Nucleotide sequences and Genes
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP methods
Qualifiers>>Measurement Properties>>AP and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular genetic observation results and disorders
Define genes and related subcellular structures by
mapped reference to scientific ontologies classified
in conjunction with SNOMED CT & LOINC Observables

13. SNOMED CT Content Extensions for MP
Substances>>Proteins
Qualifiers>>Techniques>> AP and MP methods
Qualifiers>>Measurement Properties>>AP and MP properties
Observable entity>>AP and MP observables
Clinical findings>>Anatomic and molecular genetic observation results and disorders
Define proteins and related molecular structures by
mapped reference to scientific ontologies classified
in conjunction with SNOMED CT & LOINC Observables

14. 6.1.1.5 Vet analyzed content with Observables project

15. 6.1.1.6 Deploy and test new content in Nebraska Lexicon© extension namespace

16. 6.1.1.8 Work with LOINC committee to map all Observables content to LOINC codes
As Observables content is authored in harmonized model, search RELMA to identify pre-existing LOINC codes
Submit unmapped content to LOINC committee once Observables definition agreed
Review and vet LOINC term development for semantic alignment and conformance to SNCT FSN

17. 6.1.1.9 Publish RF2 and OWL content in NLM UMLSKS

18. 6.1.1.9 Publish RF2 and OWL content in NLM UMLSKS with SNOMED CT valuesets

19. Anatomic pathology (AP) Use Case
Workplan is identical except that modelling of genes and proteins are generally not required
Extensions to Techniques and Body structures more frequent requirement for pathology services and anatomical detail

20. Anatomic pathology (AP) Use Case
Iteratively analyze semantics in CAP work sheets; define content and FSN for observables; review with iPaLM domain experts for subject matter
Extend the SNOMED CT concept model and add content in Body Structures and Substances to include genes and proteins needed for MP use case
Bind Genes and proteins by reference to NCBI ontologies and classify
Vet analyzed content with Observables project for definition; define use cases and develop consensus templates for application of concept model; document for editorial guide

21. Anatomic pathology (AP) Use Case
Workplan is identical except that modelling of genes and proteins are generally not required
Extensions to Techniques and Body structures more likely required for pathology services and anatomical detail

22. Anatomic pathology (AP): Source – CAP worksheets

23. Analyze semantics
What was the anatomic location of the tumor that was resected?

24. 6.1.1.5 Vet analyzed content with Observables project

25. 6.1.1.6 Deploy and test new content in Nebraska Lexicon© extension namespace

26. 6.1.1.8 Work with LOINC committee to map all Observables content to LOINC codes
As Observables content is authored in harmonized model, search RELMA to identify pre-existing LOINC codes
Submit unmapped content to LOINC committee once Observables definition agreed

27. 6.1.1.9 Publish RF2 and OWL content in NLM UMLSKS

28. 6.1.1.9 Publish RF2 and OWL content in NLM UMLSKS

29. Molecular Pathology Finding Fully defining observations of sequence variants

30. Patient Condition includes MP finding of tumor

31. Exemplar molecular extension concepts
Terminology development summary: CAP Colorectal and Breast Cancer checksheets
SNOMED CT
hierarchy
Anatomic Pathology
Concepts/Primitives
Molecular Genetic
Exemplar molecular extension concepts
Observable entities
61/1
32/3
“BRAF nucleotide sequence detected in excised malignancy”
Body Structures
10/9
29/3
“BRAF gene locus”
Clinical findings
6/2
7/3
“BRAF V600E variant identified in excised malignancy”
Procedures
2/1
Techniques
4/4
7/7
“Pyrosequencing”
Property types
8/8
2/2
“Sequence property”
Scale types
9/9
“Variant call format”
Situations
1/0
Substances
0/0
11/11
“BRAF human cellular protein”
Attributes
3/3
Qualifiers
TOTALS
88/29
100/41
Genes modeled for SNOMED CT/LOINC extension:
APC, BRAF, BRCA, ERBB2, ESR1, ESR2, KIT, KRAS, MKI67, MLH1,
MSH2, MSH6, NRAS, PGR, PIK3CA, PMS2, PTEN, SLC7A8
+ codons + microsatellites

32. 6.1.1.9 Publish for comment Nebraska Lexicon Publication package
Release notes
Annotated CAP protocols
Map refset: LOINC codes
Terminology refset: RF2 snapshot of Nebraska Lexicon© with LOINC codes substituted for SNCT ConceptID
(Software to load terminology refset into extension namespace of recipient)